Meiosis plays a central role in the sexual reproduction of nearly all eukaryotes. The major genetic events of recombination and chromosome segregation that occur during its two cell divisions are critical for generating genetic diversity and producing offspring with normal chromosome numbers. The overall objective of our research program is to understand the genetic mechanisms that govern meiotic development. Budding yeast is used as a model system. The specific aims of this proposal continue prior studies addressing regulation of the meiotic transcription program and progression of meiosis. Experiments are designed to determine the precise mechanism by which a key regulatory complex, Ume6/URS1, identified in our lab interacts with other proteins to both keep meiosis-specific expression off during mitosis and to turn it on in meiosis. Other regulatory sites and regulators required for Ume6- dependent, and Ume6-independent, early expression will be defined, as well as new regulators controlling the transition from early to middle gene expression. These experiments will utilize specific genetic screens based upon our recent whole genome microarray analysis of meiotic gene expression and Ume6- regulated genes. Finally, we will also take advantage of our genomic meiotic study to pursue a collaborative effort (with three other laboratories) to identify which of the meiotically- regulated genes are essential for meiotic progression. It is anticipated that this research will help uncover how critical meiotic events affecting chromosome behavior are coordinated into a successful developmental pathway. Analysis of the mechanism governing cell division and differentiation, and the factors essential for distribution of chromosomes in meiosis, should contribute significantly to understanding of cell division control, malignancy, and reproductive diseases associated with genomic instability and abnormal chromosome transmission.